-
Chemical & Pharmaceutical Bulletin 2024Two novel series of quinazolinone-based hybrids, including quinazolinone-1,3,4-oxadiazoles (10a-l) and quinazolinone-1,3,4-oxadiazole-benzimidazoles (8a-e), were...
Two novel series of quinazolinone-based hybrids, including quinazolinone-1,3,4-oxadiazoles (10a-l) and quinazolinone-1,3,4-oxadiazole-benzimidazoles (8a-e), were designed and synthesized and their cytotoxic activities against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7), were evaluated. The cytotoxic assays revealed that 10i with a lipophilic 4-fluoro-phenyl moiety at the C-2 position of the quinazolinone ring displayed good cytotoxicities against the A549 and MCF-7 cell lines, while 8b-d with the thioether-linked benzimidazole moiety incorporated on the right side of the oxadiazole ring induced comparable stronger activities toward the MCF-7 cell line, relative to the simple two-heterocycle-containing hybrid 10i. These novel quinazolinone-based hybrids could be considered as lead compounds that merit further optimization and development as anti-cancer agents.
Topics: Humans; Female; Structure-Activity Relationship; MCF-7 Cells; Antineoplastic Agents; Breast Neoplasms; Drug Screening Assays, Antitumor; Cell Proliferation; Cell Line, Tumor; Molecular Structure
PubMed: 38220213
DOI: 10.1248/cpb.c23-00674 -
The FEBS Journal Nov 2023Transglutaminase 2 (TG2), which mediates post-translational modifications of multiple intracellular enzymes, is involved in the pathogenesis and progression of cancer....
Transglutaminase 2 (TG2), which mediates post-translational modifications of multiple intracellular enzymes, is involved in the pathogenesis and progression of cancer. We used H-NMR metabolomics to study the effects of AA9, a novel TG2 inhibitor, on two breast cancer cell lines with distinct phenotypes, MCF-7 and MDA-MB-231. AA9 can promote apoptosis in both cell lines, but it is particularly effective in MD-MB-231, inhibiting transamidation reactions and decreasing cell migration and invasiveness. This metabolomics study provides evidence of a major effect of AA9 on MDA-MB-231 cells, impacting glutamate and aspartate metabolism, rather than on MCF-7 cells, characterised by choline and O-phosphocholine decrease. Interestingly, AA9 treatment induces myo-inositol alteration in both cell lines, indicating action on phosphatidylinositol metabolism, likely modulated by the G protein activity of TG2 on phospholipase C. Considering the metabolic deregulations that characterise various breast cancer subtypes, the existence of a metabolic pathway affected by AA9 further points to TG2 as a promising hot spot. The metabolomics approach provides a powerful tool to monitor the effectiveness of inhibitors and better understand the role of TG2 in cancer.
Topics: Humans; Female; Protein Glutamine gamma Glutamyltransferase 2; Breast Neoplasms; MCF-7 Cells; Apoptosis; Metabolomics; Cell Line, Tumor; Transglutaminases
PubMed: 37597264
DOI: 10.1111/febs.16931 -
Cells May 2022Breast cancer (BC) is the leading cause of death worldwide. The severity of BC strictly depends on the molecular subtype. The less aggressive hormone-positive subtype is...
BACKGROUND
Breast cancer (BC) is the leading cause of death worldwide. The severity of BC strictly depends on the molecular subtype. The less aggressive hormone-positive subtype is treated with adjuvant endocrine therapy (AET), which causes both physical and psychological side effects. This condition strongly impacts the adherence and persistence of AET among oncologic patients. Moreover, viral infections also constitute a serious problem for public health. Despite their efficacy, antiviral agents present several therapeutic limits. Accordingly, in the present work, we investigated the antitumor and antiviral activities of Forssk. (), a parasitic plant, endemic to the Mediterranean basin, traditionally known for its beneficial properties for human health.
METHODS
The MTT assay was carried out to evaluate the cytotoxic effect of leaf extract (OCLE) on human breast cancer cells (MCF-7 and MDA-MB-231) and the primary HFF-1 cell line. The lactic dehydrogenase (LDH) assay was performed on MCF-7 cells to analyze necrotic cell death. The antioxidant effect of OCLE was evaluated by intracellular determination of the reactive oxygen species and thiol groups, by DPPH and ABTS assays. The antiviral activity of OCLE was determined against 1, 9, Human respiratory syncytial virus, type 2 and type 5, B1 (CoxB1) and B3 (CoxB3), type 1 (HSV-1) and type 2 (HSV-2), and β- by the plaque reduction assay.
RESULTS
The extract, after 24 h of incubation, did not affect MDA-MB-231 and HFF-1 cell viability. However, at the same time point, it showed a dose-dependent inhibitory effect on MCF-7 cells, with an increase in LDH release. OCLE exhibited free radical scavenging activity and significantly increased non-protein thiol levels in MCF-7 cells. OCLE effectively inhibited HSV-1, HSV-2, CoxB1, and CoxB3 replication.
CONCLUSIONS
The overall results showed an interesting inhibitory effect of OCLE on both MCF-7 cell survival and viral replication.
Topics: Female; Humans; Antiviral Agents; Breast Neoplasms; Herpesvirus 1, Human; MCF-7 Cells; Orobanche; Plant Extracts; Sulfhydryl Compounds; Virus Replication
PubMed: 35626733
DOI: 10.3390/cells11101696 -
International Journal of Environmental... Jun 2023() is an endemic species of Tunceli region of Turkey. In this study, we investigated anticancer effect of aqueous extract of (OME) on breast cancer cells (MCF-7)....
() is an endemic species of Tunceli region of Turkey. In this study, we investigated anticancer effect of aqueous extract of (OME) on breast cancer cells (MCF-7). cytotoxic effect of OME was evaluated in MCF-7 cells by MTT assay. The wound-healing assay was used to examine the inhibition of migration. Annexin V/propidium iodide staining, cell-cycle distribution was assessed by flow cytometry for MCF-7 cells treated with OME. MTT results show that OME demonstrated in vitro cytotoxicity with 600 mg at 48 h on MCF-7. Doses of 400 µg/mL and 600 µg/mL OME significantly suppressed the migration rate of MCF-7 cells. OME significantly decreased the percentage of live cancer cells and showed an apoptotic effect after 48 h of incubation. These results show that OME is effective against breast cancer when administered at high doses and for a long time.
Topics: Humans; Female; MCF-7 Cells; Breast Neoplasms; Origanum; Plant Extracts; Apoptosis
PubMed: 35188839
DOI: 10.1080/09603123.2022.2042495 -
Journal of Natural Products Nov 2023Eleven new phenyltetracenoid polyketides, streptovertimycins U () and V (), 14-bromo-streptovertidione (), streptovertimycins W-Y (-), and streptovertimycins Z-Z (-,...
Eleven new phenyltetracenoid polyketides, streptovertimycins U () and V (), 14-bromo-streptovertidione (), streptovertimycins W-Y (-), and streptovertimycins Z-Z (-, together with the known congeners fasamycins R () and S () and accramycins A () and B (), were isolated from the NaBr-supplemented rice-grown cultures of SC1169. Their structures were elucidated by extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and theoretical computations of ECD spectra. Compounds and are methylene-bridged dimers of accramycin A, and compounds and - are brominated fasamycin congeners. Compounds and - exhibited activity against the drug-resistant bacteria MRSA and VRE (MIC = 0.6-5.0 μg/mL), and the dimer displayed activity against MRSA (MIC = 2.5 μg/mL). Compounds - showed cytotoxicity against the human carcinoma A549, HeLa, HepG2, and MCF-7 cells in the IC range between 1.7 and 9.2 μM.
Topics: Humans; Streptomyces; HeLa Cells; Spectrum Analysis; MCF-7 Cells; Anti-Bacterial Agents; Molecular Structure
PubMed: 37947788
DOI: 10.1021/acs.jnatprod.3c00788 -
Natural Product Research Dec 2021Secoisolariciresinol diglucoside (SDG) is isolated from seeds. The antiproliferative effects of SDG and its derivatives secoisolariciresinol and...
Secoisolariciresinol diglucoside (SDG) is isolated from seeds. The antiproliferative effects of SDG and its derivatives secoisolariciresinol and secoisolariciresinol-4', 4″-diacetate ( have been evaluated on MCF-7 breast cancer cells and normal breast epithelial line MCF-10A. Lignan has not shown cytotoxic effects on MCF-7 cells, while derivatives and have inhibited cell growth with IC values of 25 and 11 µM, respectively. Estrogen receptor alpha is a key growth driver in MCF-7 cells. Compound did not affect the activity of ERα, while derivatives and showed significant antiestrogenic effects. Compounds and caused apoptosis in the MCF-7 line, determined by the cleavage of PARP. SDG derivative enhanced the effect of doxorubicin. SDG derivatives can be considered as promising agents that exhibit a combined antiestrogen and proapoptotic effect in hormone-dependent breast cancer cells.
Topics: Breast Neoplasms; Butylene Glycols; Female; Flax; Glucosides; Humans; Lignans; MCF-7 Cells
PubMed: 33025821
DOI: 10.1080/14786419.2020.1826479 -
Analytical Chemistry Jan 2020Profiling the kinetics of cell-matrix adhesion is of great importance to understand many physiological and pathological processes such as morphogenesis, tissue...
Profiling the kinetics of cell-matrix adhesion is of great importance to understand many physiological and pathological processes such as morphogenesis, tissue homeostasis, wound healing, and tumorigenesis. Here, we developed a novel digital acoustofluidic device for parallel profiling cell-matrix adhesion at single-cell level. By introduction of localized and uniform acoustic streaming into an open chamber microfluidic device, the adherent cells within the open chamber can be detached by the streaming-induced Stokes drag force. By digital regulation of pulsed acoustic power from a low level to high levels, the hundreds of adherent cells can be ruptured from the fibronectin-coated substrate accordingly, and their adhesive forces (from several pN to several nN) and kinetics can be determined by the applied power and cell incubation time. As a proof-of-concept application for studying cancer metastasis, we applied this technique to measure the adhesion strength and kinetics of human breast cancer cells to extracellular matrix such as fibronectin and compared their metastatic potentials by measuring the rupture force of cancer cells representing malignant (MCF-7 cells and MDA-MB-231 cells) and nonmalignant (MCF-10A cells) states. Our acoustofluidic device is simple, easy to operate, and capable of measuring, in parallel, hundreds of individual cells' adhesion forces with a resolution at the pN level. Thus, we expect this device could be widely used for both fundamental cell biology research as well as development of cancer diagnostics and tissue engineering technologies.
Topics: Acoustics; Cell Adhesion; Cell-Matrix Junctions; Cells, Cultured; Equipment Design; Humans; Kinetics; MCF-7 Cells; Microfluidic Analytical Techniques
PubMed: 31880433
DOI: 10.1021/acs.analchem.9b05065 -
Archives of Razi Institute 2021Conventional cancer treatments are costly and have different serious side effects for patients. Natural herbal treatments are widely accepted among people because of...
Conventional cancer treatments are costly and have different serious side effects for patients. Natural herbal treatments are widely accepted among people because of their minimal side effects, although there is little scientific knowledge about them. One of these remedies utilizes the root of that has been used for years in Iran to treat different chronic genital diseases. The current study examined the effects of methanolic and ethanolic extracts of (induction of necrosis and apoptosis) on breast cancer (MCF-7), ovarian cancer (A2780), and human cervix cancer (HeLa) cell lines in comparison with normal breast cells. These effects were determined to be morphological alterations in cell light microscopy, by flow cytometry (staining with annexin V and propidium iodide), and by measuring live cells and inhibition concentrations by MTT assay. IC50 of on the MCF-7 cell line (methanolic extract) was 400 µg/ml and for A2780 was 250 µg/ml. The IC50 amount of on the MCF-7 cell line (ethanolic extract) was 750 µg/ml and 1500 for A2780. Results demonstrated that apoptosis and necrosis occurred in MCF-7 and A2780 following the addition of ethanolic and methanolic extracts of to the medium. These findings confirmed the anti-cancer effects of mehthanolic extracts of root and its safety for normal cells; thus, it can be applied in cancer therapy as a novel medication.
Topics: Cell Line, Tumor; Female; HeLa Cells; Humans; MCF-7 Cells; Ovarian Neoplasms; Plant Extracts
PubMed: 34824753
DOI: 10.22092/ari.2020.351952.1545 -
Biomaterials Advances Dec 2022Biocompatible polymers have received significant interest from researchers for their potential in diagnostic applications. This type of polymer can perform with an...
Biocompatible polymers have received significant interest from researchers for their potential in diagnostic applications. This type of polymer can perform with an appropriate host response or carrier for a specific purpose. The current study aims to fabricate and characterise poly(ethylene) oxide (PEO) nanofibres with different concentrations for cytotoxicity evaluation in human breast cancer cell lines (MCF-7) and to get an optimal PEO nanofibre concentration (permissible limit) as a suitable polymer matrix or carrier with potential use in diagnostic applications. The fabrication of PEO nanofibres was done using electrospinning and was characterised by structure and morphology, surface roughness, chemical bonding and release profiles. The functional effects of PEO nanofibres were evaluated with MTS assay and colony formation assay in MCF-7 cells. The results showed that viscosity plays a vital role in synthesising a polymer solution in electrospinning for producing beadless nanofibrous mats ranging from 4.7 Pa·s to 77.7 Pa·s. As the PEO concentration increases, the nanofibre diameter and thickness will increase, but the surface roughness will be decreased. The average fibre diameter for 5 wt% PEO, 6 wt% PEO and 7 wt% PEO nanofibres were 129 ± 70 nm, 185 ± 55 nm and 192 ± 53 nm, respectively. In addition, the fibre thickness for 4 wt% PEO, 5 wt% PEO, 6 wt% PEO and 7 wt% PEO nanofibres were 269 ± 3 μm, 664 ± 4 μm, 758 ± 7 μm and 1329 ± 44 μm, respectively. Contrarily, the surface roughness for 4 wt% PEO, 5 wt% PEO, 6 wt% PEO and 7 wt% PEO nanofibres were 55.6 ± 9 nm, 42.8 ± 6 nm, 42.7 ± 7 nm and 36.6 ± 1 nm, respectively. PEO nanofibres showed the same burst release pattern and rate due to the same molecular weight of PEO with a stable release rate profile after 15 min. It also demonstrates that the percentage of PEO nanofibre release increased with the increasing PEO concentration due to the fibre diameter and thickness. The findings showed that all PEO nanofibres formulations were non-toxic to MCF-7 cells. It is suggested that 5 wt% PEO nanofibre exhibited non-cytotoxic characteristics by maintaining the cell viability from dose 0-1000 μg/ml and did not induce the number of colonies. Therefore, 5 wt% PEO nanofibre is the optimal nanofibre concentration and was suggested as a suitable base polymer matrix or carrier with potential use for diagnostic purposes. The findings in this study have demonstrated the influence of cell growth and viability, including the effects of PEO nanofibre formulations on cancer progress characteristics to achieve a permissible PEO nanofibre concentration limit that can be a benchmark in medical applications, particularly diagnostic applications.
Topics: Humans; Female; Nanofibers; Polyethylene Glycols; MCF-7 Cells; Breast Neoplasms; Polymers; Ethylenes; Oxides
PubMed: 36368056
DOI: 10.1016/j.bioadv.2022.213178 -
Langmuir : the ACS Journal of Surfaces... Jan 2022The connection between cells and their substrate is essential for biological processes such as cell migration. Atomic force microscopy nanoindentation has often been...
The connection between cells and their substrate is essential for biological processes such as cell migration. Atomic force microscopy nanoindentation has often been adopted to measure single-cell mechanics. Very recently, fluidic force microscopy has been developed to enable rapid measurements of cell adhesion. However, simultaneous characterization of the cell-to-material adhesion and viscoelastic properties of the same cell is challenging. In this study, we present a new approach to simultaneously determine these properties for single cells, using fluidic force microscopy. For MCF-7 cells grown on tissue-culture-treated polystyrene surfaces, we found that the adhesive force and adhesion energy were correlated for each cell. Well-spread cells tended to have stronger adhesion, which may be due to the greater area of the contact between cellular adhesion receptors and the surface. By contrast, the viscoelastic properties of MCF-7 cells cultured on the same surface appeared to have little dependence on cell shape. This methodology provides an integrated approach to better understand the biophysics of multiple cell types.
Topics: Biophysics; Cell Adhesion; Humans; MCF-7 Cells; Microscopy, Atomic Force; Surface Properties
PubMed: 34981921
DOI: 10.1021/acs.langmuir.1c01973